Anti-tumour immune responses to modified self-epitopes

Abstract

The present invention relates to modified citrullinated enolase peptides that can be used as targets for cancer immunotherapy. These peptides can be used as vaccines or as targets for monoclonal antibody (mAb) therapy. Such vaccines or mAbs may be used in the treatment of cancer.

The invention claimed is: 
     
       1. A method for the treatment of cancer in a subject in need thereof comprising administering to the subject a citrullinated peptide comprising, consisting essentially of, or consisting of:
 i) an amino acid sequence selected from the group consisting of: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   VIGMDVAASEFFcitSGKYDLD, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   VIGMDVAASEFYcitSGKYDLD, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   EVDLFTSKGLFcitAAVPSGAS, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   EVDLYTAKGLFcitAAVPSGAS, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   KGVPLYcitHIADLAGNSEVIL, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   KGVPLYcitHIADLAGNPEVIL, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   VGDDLTVTNPKcitIAKAVNEK, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   VGDDLTVTNPKcitIAKAASEK, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   IFDScitGNPTVEVDLF, 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   IFDScitGNPTVEVDLY. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein “cit” represents citrulline, or 
         ii) the amino acid sequence of i), with the exception of 1, 2 or 3 amino acid substitutions, and/or 1, 2 or 3 amino acid insertions, and/or 1, 2 or 3 amino acid deletions in a non-citrulline position. 
       
     
     
       2. The method of  claim 1 , wherein the cancer is breast cancer, colorectal cancer, gastric cancer, non-small cell lung cancer, ovarian cancer, endometrial carcinoma, pancreatic cancer, leukaemia, melanoma, head and neck cancer or lung cancer. 
     
     
       3. The method  claim 1 , wherein the subject is a human or non-human animal. 
     
     
       4. The method of  claim 1 , wherein the citrullinated peptide is administered as a pharmaceutical composition comprising the peptide in combination with a pharmaceutically acceptable carrier. 
     
     
       5. The method of  claim 3 , wherein the subject is a human. 
     
     
       6. The method of  claim 5 , wherein the subject expresses HLA-DP4. 
     
     
       7. The method of  claim 2 , wherein the cancer is breast cancer. 
     
     
       8. The method of  claim 7 , wherein the cancer is estrogen receptor negative breast cancer. 
     
     
       9. The method of  claim 2 , wherein the cancer is ovarian cancer. 
     
     
       10. The method of  claim 2 , wherein the cancer is pancreatic cancer. 
     
     
       11. The method of  claim 10 , wherein pancreatic cancer is pancreatic ductal adenocarcinoma. 
     
     
       12. The method of  claim 1 , wherein the citrullinated peptide comprises the amino acid sequence VIGMDVAASEFFcitSGKYDLD (SEQ ID NO: 1), wherein “cit” represents citrulline. 
     
     
       13. The method of  claim 1 , wherein the citrullinated peptide consists essentially of the amino acid sequence VIGMDVAASEFFcitSGKYDLD (SEQ ID NO: 1), wherein “cit” represents citrulline. 
     
     
       14. The method of  claim 1 , wherein the citrullinated peptide consists of the amino acid sequence VIGMDVAASEFFcitSGKYDLD (SEQ ID NO: 1), wherein “cit” represents citrulline.